The lacrimal gland forms a serous secretion which composes the greater part of the tears and helps maintain the epithelial cells of the cornea. In aged individuals the secretion of the lacrimal gland decreases and its composition of solutes also changes. These changes often result in the inability of the tears to maintain the cornea, resulting in keratoconjunctivitis sicca, dry eyes. If inadequately treated, dry eyes may result in the deterioration of the cornea and loss of vision or even blindness. The physiological mechanisms of lacrimal protein secretion are only poorly understood; the changes that result in dry eyes are understood even less. The general aim of this study is to develop an understanding of the basic physiological mechanisms of lacrimal protein secretion. Further, this study seeks to determine what changes occur in aging that can account for the diminished secretory activity that is detrimental to the health and well being of the cornea. This project seeks to answer 5 specific questions: (1) Does aging alter the physiological responsiveness to autonomic and peptidergic agonists in a uniform or selective manner? (2) Do the types of protein secreted in response to autonomic and peptidergic agonists change with age? (3) Are females more susceptible to age-related changes than males? (4) Are the lacrimal secretory changes associated with aging due only to lowered maximum responses or are entire dose-response curves shifted for each autonomic or peptidergic agonist? (5) Do the number and affinity of membrane-bound autonomic receptors change in association with the observed physiological changes? Lacrimal gland fragments from 4, 24 and 30 month old male and female F344 rats will be placed in perifusion chambers and stimulated with autonomic and peptidergic agonists. The perifusate will be assayed for secreted protein and peroxidase content. Dose-response curves will be constructed for each group of animals. Gel electrophoresis will be used to determine if the secreted proteins change with age. Age and sex-dependent changes in responsiveness or in the kinds of proteins secreted will be correlated with changes in the autonomic receptors of the cell membrane. By determining what age-related changes occur, it may be possible to design therapy that will assist the aged lacrimal gland in secreting fluid of the proper composition.